<br>ZIF-8 封装的 Pexidartinib 通过靶向肽修饰的 M1 巨噬细胞递送可减弱骨肉瘤中 MDSC 介导的免疫抑制,Small

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ZIF-8 封装的 Pexidartinib 通过靶向肽修饰的 M1 巨噬细胞递送可减弱骨肉瘤中 MDSC 介导的免疫抑制
Small ( IF 13.0 ) Pub Date : 2024-03-08 , DOI: 10.1002/smll.202309038
Jiabao Dong ₁ , Xupeng Chai ₂ , Yucheng Xue ₂ , Shiyun Shen ₁ , Zhuo Chen ₁ , Zetao Wang ₁ , Eloy Yinwang ₂ , Shengdong Wang ₂ , Liang Chen ₂ , Fengfeng Wu ₁ , Hengyuan Li ₂ , Zehao Chen ₂ , Jianbin Xu ₂ , Zhaoming Ye ₂ , Xiongfeng Li ₁ , Qian Lu ₁

Affiliation

过继细胞疗法是一种有前途的癌症治疗策略。然而，这种疗法的有效性受到其复杂且免疫抑制的肿瘤微环境的限制。在这项研究中，提出了巨噬细胞负载药物的靶向治疗策略，以增强巨噬细胞的抗肿瘤功效。 K7M2 靶肽 (KTP) 用于修饰巨噬细胞以增强其对肿瘤的亲和力。将负载 Pexidartinib 的 ZIF-8 纳米颗粒（P@ZIF-8）加载到巨噬细胞中，可协同缓解免疫抑制的肿瘤微环境。因此，用KTP修饰的M1巨噬细胞携带P@ZIF-8并命名为P@ZIF/M1-KTP。 P@ZIF/M1-KTP组的肿瘤体积明显小于其他组，表明P@ZIF/M1-KTP表现出增强的抗肿瘤功效。从机制上讲，P@ZIF/M1-KTP治疗后肿瘤组织中CD4+ T细胞比例增加，MDSCs比例下降，表明它可以缓解免疫抑制的肿瘤微环境。 RNA-seq进一步证实了增强的免疫细胞功能。因此，P@ZIF/M1-KTP 作为一种新型的过继性肿瘤细胞治疗策略具有巨大的潜力。

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ZIF-8-Encapsulated Pexidartinib Delivery via Targeted Peptide-Modified M1 Macrophages Attenuates MDSC-Mediated Immunosuppression in Osteosarcoma

Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1-KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.

更新日期：2024-03-08

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